JP2017531637A - プレガバリン徐放性製剤 - Google Patents
プレガバリン徐放性製剤 Download PDFInfo
- Publication number
- JP2017531637A JP2017531637A JP2017517340A JP2017517340A JP2017531637A JP 2017531637 A JP2017531637 A JP 2017531637A JP 2017517340 A JP2017517340 A JP 2017517340A JP 2017517340 A JP2017517340 A JP 2017517340A JP 2017531637 A JP2017531637 A JP 2017531637A
- Authority
- JP
- Japan
- Prior art keywords
- sustained
- release preparation
- oral
- release
- alginate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 title claims abstract description 36
- 229960001233 pregabalin Drugs 0.000 title claims abstract description 33
- 239000003405 delayed action preparation Substances 0.000 title claims abstract description 26
- 235000010443 alginic acid Nutrition 0.000 claims abstract description 21
- 229920000615 alginic acid Polymers 0.000 claims abstract description 21
- 239000007939 sustained release tablet Substances 0.000 claims abstract description 16
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 13
- -1 polyoxyethylene Polymers 0.000 claims abstract description 12
- 239000000126 substance Substances 0.000 claims abstract description 11
- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 33
- 238000009472 formulation Methods 0.000 claims description 30
- 239000011159 matrix material Substances 0.000 claims description 21
- 230000008961 swelling Effects 0.000 claims description 21
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 17
- 229940072056 alginate Drugs 0.000 claims description 17
- 238000013268 sustained release Methods 0.000 claims description 16
- 239000012730 sustained-release form Substances 0.000 claims description 16
- 210000002784 stomach Anatomy 0.000 claims description 13
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 8
- 159000000007 calcium salts Chemical class 0.000 claims description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 230000036470 plasma concentration Effects 0.000 claims description 5
- 235000010216 calcium carbonate Nutrition 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 3
- 230000000717 retained effect Effects 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- 235000010407 ammonium alginate Nutrition 0.000 claims description 2
- 239000000728 ammonium alginate Substances 0.000 claims description 2
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 claims description 2
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 2
- 229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 235000011132 calcium sulphate Nutrition 0.000 claims description 2
- JXRVKYBCWUJJBP-UHFFFAOYSA-L calcium;hydrogen sulfate Chemical compound [Ca+2].OS([O-])(=O)=O.OS([O-])(=O)=O JXRVKYBCWUJJBP-UHFFFAOYSA-L 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 235000010408 potassium alginate Nutrition 0.000 claims description 2
- 239000000737 potassium alginate Substances 0.000 claims description 2
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 abstract description 2
- 229960001126 alginic acid Drugs 0.000 abstract description 2
- 150000004781 alginic acids Chemical class 0.000 abstract description 2
- 239000000470 constituent Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 35
- 239000003814 drug Substances 0.000 description 31
- 229940079593 drug Drugs 0.000 description 30
- 239000000499 gel Substances 0.000 description 19
- 238000007922 dissolution test Methods 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 239000000463 material Substances 0.000 description 10
- 238000004090 dissolution Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
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- 239000002609 medium Substances 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 6
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- 210000000813 small intestine Anatomy 0.000 description 5
- 239000002775 capsule Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
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- 239000004615 ingredient Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 210000004051 gastric juice Anatomy 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 210000001187 pylorus Anatomy 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229940009697 lyrica Drugs 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000013341 scale-up Methods 0.000 description 2
- AEMOLEFTQBMNLQ-AZLKCVHYSA-N (2r,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-AZLKCVHYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-SYJWYVCOSA-N (2s,3s,4s,5s,6r)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-SYJWYVCOSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 206010061334 Partial seizures Diseases 0.000 description 1
- 241000199919 Phaeophyceae Species 0.000 description 1
- 229920003072 Plasdone™ povidone Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000001815 ascending colon Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 235000010410 calcium alginate Nutrition 0.000 description 1
- 239000000648 calcium alginate Substances 0.000 description 1
- 229960002681 calcium alginate Drugs 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- LVGQIQHJMRUCRM-UHFFFAOYSA-L calcium bisulfite Chemical compound [Ca+2].OS([O-])=O.OS([O-])=O LVGQIQHJMRUCRM-UHFFFAOYSA-L 0.000 description 1
- 229940062672 calcium dihydrogen phosphate Drugs 0.000 description 1
- 235000010260 calcium hydrogen sulphite Nutrition 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
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- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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Abstract
Description
膨潤物質は胃液から水を吸収し、元の容積の数倍に膨潤して、サイズ排除のため徐放性錠剤の胃保持をもたらし、そして親水性コロイドを形成することによって薬物放出速度にも影響する。膨潤物質は水に溶解性でも不溶性でもよい。膨潤物質の量は、徐放性錠剤の全重量に対して、重量で約10%〜75%、好ましくは約30%〜60%、より好ましくは約35%〜60%である。本発明の膨潤物質としては、ポリエチレンオキシドやポリエチレングリコールとしても知られるポリオキシエチレンが挙げられる。ポリオキシエチレンの分子量は1×105 〜1×107、好ましくは1×106 〜1×107である。
本発明を以下の実施例および試験例によってより詳細に説明する。これらの実施例および試験例は説明するためだけのものであり、本発明の範囲を限定するものではない。
実施例1〜20
実施例1〜21および比較例1で調製した錠剤を中国薬局方(2010年版)第II巻の付録に開示の溶出試験の第2法(パドル法)により溶出試験に付した。0.06 N HCl溶液1000 mlを溶出媒体として用い、溶出試験を37±0.5°Cおよびパドルスピード50 rpmで行った。少量のサンプルを、それぞれ0.5, 1, 2, 4, 8, 12, 16, 20および24時間で溶出媒体から採取した。各サンプルはHPLC(210 nmで)分析し、溶出率を計算した。結果は表5〜7に示した。
表5〜7に示したように、本発明に従って調製したプレガバリン製剤は優れた徐放性放出パターンを示した。徐放性製剤の成分と比率を調節することにより、プレガバリン徐放性製剤は本質的に1時間でバースト放出効果は持たず、8時間で溶出量は50%〜70%、そして16時間で放出量は80%以上であった。比較例1で調製した錠剤は1時間で約20%の累積溶出率を持ち、一定のバースト放出効果を示したが、一方本発明に従って調製した錠剤はこのバースト放出効果は著しく弱められ、それによりプレガバリンがより穏やかに放出されて、薬物の安全性が増していた。
上記実施例および比較例で調製した錠剤を中国薬局方(2010年版)第II巻の付録に開示の溶出試験の第2法(パドル法)により溶出試験に付した。0.06 N HCl溶液1000 mlを溶出媒体として用い、溶出試験を37±0.5°Cおよびパドルスピード50 rpmで行った。薬剤サンプルを溶出試験の開始から1, 2, 6, 8および24時間で溶出媒体から採取し、次いでそれらのサイズを測定した。結果は表8および9に示した。本発明により調製した錠剤のサイズは、1時間で13mm以上に膨潤した(「サイズ」は剤形の最も小さな面積を持つ断面の最も長い直線サイズに相当する)。徐放性錠剤の胃での滞留時間は、大きさによる機械的な遅延によって効果的に延長できている。比較例1で調製した錠剤のサイズは1時間で11.4mmに膨潤しただけで、幽門を通過する可能性は患者の消化管の状態により排除できなかった。
実施例6,7および比較例1で調製した錠剤を中国薬局方(2010年版)第II巻の付録に開示の溶出試験の第2法(パドル法)により溶出試験に付した。0.06 N HCl溶液1000 mlを溶出媒体として用い、溶出試験を37±0.5°Cおよびパドルスピード50 rpmで行った。薬剤サンプルを溶出試験の開始から1, 2, 6, 8および24時間で溶出媒体から採取した;それらのサイズを測定し、各錠剤の重量変化をその水分含量を測定することにより得た。結果は表10に示した。
表10に見られるように、実施例1および7で調製した錠剤は、比較例1の錠剤に比べ、サイズ変化と水分含量でより優れた特性を示した。これらの結果は、本発明の錠剤は胃での滞留時間をより効果的に増大させ、それにより薬物の長く続く放出と吸収を達成して、薬剤のバイオアベイラビリティを改善することを示した。
実施例7および比較例1で調製した錠剤を中国薬局方(2010年版)第II巻の付録に開示の溶出試験の第2法(パドル法)により溶出試験に付した。0.06 N HCl溶液1000 mlを溶出媒体として用い、溶出試験を37±0.5°Cおよびパドルスピード50 rpmで行った。薬剤サンプルを溶出試験の開始から1, 2, 6, 8および24時間で溶出媒体から採取し、それらの硬度をTA-Plusテクスチャーアナライザーを用いて以下:5 kg load unit; P/0.5 cylindrical probe; 1.0 g trigger force; 1.0 mm/s test speed; 15 mm distanceのセッティング条件下で測定した。結果を表11に示した。
表11に見られるように、本発明(実施例1および7)により調製した錠剤は、比較例1の錠剤に比べ、より優れた硬度を持ち、さらに8時間および24時間の膨潤後も良い硬度を示した。優れた硬度はその良い胃保持特性を示し、一方でプレガバリンの放出のコントロールに効果的であった。
実施例1、7および比較例1で調製した錠剤を中国薬局方(2010年版)第II巻の付録に開示の溶出試験の第2法(パドル法)により溶出試験に付した。0.06 N HCl溶液1000 mlを溶出媒体として用い、溶出試験を37±0.5°Cおよびそれぞれ50 rpmおよび100 rpmのパドルスピードで行った。少量のサンプルを、それぞれ0.5, 1, 2, 4および8時間で溶出媒体から採取した。各サンプルはHPLC(210 nmで)分析して、溶出率を計算した。結果は表12に示した。
実施例14で調製した錠剤の薬物動態試験はビーグル犬を用いて行った。市販のLyrica(登録商標) カプセル300 mg (Pfizer Pharmaceutical Co., Ltd.)を対照製剤として用いた。血漿中プレガバリン濃度は液体クロマトグラフィー‐タンデム質量分析法により測定した。血漿濃度曲線は図1に示した;薬物動態パラメータは表13に示した。
Claims (15)
- ゲルマトリックス物質がアルギン酸塩から成り、膨潤物質がポリオキシエチレンから成る、活性成分としてのプレガバリンまたはその塩または水和物、ゲルマトリックス物質および膨潤物質を含有する経口用徐放性製剤。
- 1日1回経口投与される、請求項1に記載の経口用徐放性製剤。
- アルギン酸塩がアルギン酸ナトリウム、アルギン酸カリウム、およびアルギン酸アンモニウムの1以上から選択される、請求項1に記載の経口用徐放性製剤。
- ゲルマトリックス物質の量が徐放性製剤の全重量に対して重量で5%〜45%、好ましくは20%〜40%である、請求項1に記載の経口用徐放性製剤。
- 膨潤物質の量が徐放性錠剤の全重量に対して重量で、10%〜75%、好ましくは30%〜60%、より好ましくは35%〜60%である、請求項1に記載の経口用徐放性製剤。
- アルギン酸塩の平均分子量が1×104 〜2×105、好ましくは7×104 〜15×104である、請求項1に記載の経口用徐放性製剤。
- ポリオキシエチレンの平均分子量が1×105 〜1×107、好ましくは1×106 〜1×107である、請求項1に記載の経口用徐放性製剤。
- ゲルマトリックス物質が好ましくはリン酸水素カルシウム、リン酸カルシウム、硫酸水素カルシウム、硫酸カルシウム、炭酸水素カルシウム、炭酸カルシウムおよび塩化カルシウムの1以上から選択されるカルシウム塩を更に含有する、請求項1に記載の経口用徐放性製剤。
- アルギン酸塩のカルシウム塩に対する重量比が1: 1〜10: 1、好ましくは2: 1〜5: 1である、請求項8に記載の経口用徐放性製剤。
- 膨潤剤が更に架橋ポリビニルピロリドンを含有する、請求項1に記載の経口用徐放性製剤。
- 膨潤剤がポリオキシエチレンと架橋ポリビニルピロリドンから成る、請求項10に記載の経口用徐放性製剤。
- ポリオキシエチレンが製剤の全重量に対して、重量で25%〜55%、好ましくは30%〜50%の量で存在し;架橋ポリビニルピロリドンが製剤の全重量に対して、重量で5%〜20%、好ましくは5%〜10%の量で存在する、請求項9または10に記載の経口用徐放性製剤。
- 徐放性製剤が水と接触したときに13mm以上のサイズに膨張してもよい、請求項1に記載の経口用徐放性製剤。
- 徐放性製剤が経口投与後3時間〜14時間患者の胃に保持される、請求項1に記載の経口用徐放性製剤。
- 最大血漿中濃度までの時間(Tmax)が徐放性製剤の経口投与後8時間〜12時間である、請求項1に記載の経口用徐放性製剤。
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JPWO2019146642A1 (ja) * | 2018-01-24 | 2020-12-10 | 大原薬品工業株式会社 | γ−アミノ酪酸誘導体含有錠剤の化学的安定性を改善する方法 |
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